Issaquena County is a county located in the U.S. state of Mississippi. As of the 2020 Census, its population was 1,338, making it the least populous county in the United States east of the Mississippi River. Its county seat is Mayersville. With a per-capita income of $18,598, Issaquena County is, by that measure, one of the poorest counties in the United States. Issaquena County is located in the Mississippi Delta region. The Mississippi River flows along the entire western boundary of the county, and many of the earliest communities were river ports. The county's economy is chiefly based on agriculture, though a number of hunting camps are also located here and contribute to the economy. Mississippi's two most recent records for the heaviest alligator taken by a hunter have both been in Issaquena County, the latest in 2012 when a 697.5 lb alligator was killed at a camp near Fitler.

Agency Contact Information